Rapid PROTAC Discovery Platform: Nanomole-Scale Array Synthesis and Direct Screening of Reaction Mixtures.

Precise length, shape, and linker attachment points are all integral components to designing efficacious proteolysis targeting chimeras (PROTACs). Due to the synthetic complexity of these heterobifunctional degraders and the difficulty of computational modeling to aid PROTAC design, the exploration of structure-activity relationships remains mostly empirical, which requires a significant investment of time and resources. To facilitate rapid hit finding, we developed capabilities for PROTAC parallel synthesis and purification by harnessing an array of preformed E3-ligand-linker intermediates.

hiPSC-Derived Epidermal Keratinocytes from Ichthyosis Patients Show Altered Expression of Cornification Markers.

Inherited ichthyoses represent a large heterogeneous group of skin disorders characterised by impaired epidermal barrier function and disturbed cornification. Current knowledge about disease mechanisms has been uncovered mainly through the use of mouse models or human skin organotypic models. However, most mouse lines suffer from severe epidermal barrier defects causing neonatal death and human keratinocytes have very limited proliferation ability in vitro.

Wavering enthusiasm.

This reflection focuses on an experience I had whilst on my community placement involving my first birth, a home birth. I attended as a student midwife. In order to maintain confidentiality I have used pseudonyms throughout.

School-entry vision screening in the United Kingdom: practical aspects and outcomes.

Purpose: To describe and assess an orthoptist-led vision screening service for school-entry (reception class) children, and report outcomes from one healthcare trust in the UK.

Methods: A total of 3721 children (aged 4-5 years) in reception class primary school (155 state, 3 private) underwent orthoptist-conducted vision screening. Children who failed to meet the screening criteria were referred to hospital-based eye services for re-testing and final diagnosis.

Physical modelling of solute transport in porous media: evaluation of an imaging technique using UV excited fluorescent dye.

The development and evaluation of a 2-dimensional physical model, which is designed to assist in the characterisation of complex solute transport problems in porous media, is described. The laboratory model is a transparent 2-dimensional porous media of nominal thickness and uses a non-invasive imaging technique in conjunction with a fluorescent dye tracer (sodium fluorescein) to monitor solute movements. Under ultraviolet (UV) illumination the dye emits visible light which is imaged by a CCD (Charge Coupled Device) camera.